Immunotherapy represents a promising approach to prostate cancer treatment. Recent data from our laboratory (as well as others) shows that the immune checkpoint mediated by interactions between the T cell surface molecule known as PD-1 and the molecule B7-H1 on cancer cells can inhibit an anti-tumor immune response. Thus, blockade of this interaction using monoclonal antibodies directed against PD-1 may play a role in prostate cancer treatment. Our group has also shown that anti-cancer vaccines based on attenuated Listeria Monocytogenes (LM) show a striking synergy with blockade of the PD-1 / B7-H1 checkpoint. Thus, we propose a Phase I trial combining these two agents for men with prostate cancer. Because disease burden plays a major role in the outcome of immunotherapy, we have chosen to target men with minimal disease, i.e. men who have undergone radiation therapy for high-risk disease. Both of the agents employed here are currently in Phase I testing, and those data will be used to fine-tune the combinatorial approach. The trial includes several critical immune correlates to test the central hypothesis that the combination of PD-1 blockade and PSCA-specific LM-based vaccination will break tolerance and result in the accumulation of activated CDS T cells in the prostate gland. If successful and well tolerated, a larger phase II trial with relevant clinical endpoints will be initiated.